To date, the DSF has allocated over $1,000,000 to the following research projects:
2011 Awards
Jack M. Parent, MD
DSF Research Award – $250,000 (2 year project)
Readthrough Treatment of Dravet Syndrome Caused by Nonsense SCN1A Mutations
Dr. Parent and collaborators Dr. Lori Isom and Dr. Miriam Meisler will investigate whether readthrough therapy is a clinically viable treatment for Dravet syndrome patients who carry stop codon nonsense mutations. With a new technique, the induced pluripotent stem cell (iPSC) method, they have a unique opportunity to study the effects of mutations in neural cells by deriving neurons from patients’ own skin cells. In addition, they will collaborate with Dr. Richard Gatti, a Professor of Human Genetics at UCLA, who is developing new and improved readthrough compounds. Parent and his colleagues will test whether gentamicin, PTC124, or newer compounds will increase normal sodium channel levels and restore channel function in patient-derived neurons. They will also examine whether mice with a Dravet syndrome knock-in premature termination (stop) codon nonsense mutation (a point mutation in a sequence of DNA) will respond to readthrough therapy with a decrease in seizures and normalization of sodium channel function.
Scott Baraban, PhD
DSF Research Award – $100,000 (1 year project)
Drug Discovery in a Zebrafish Model of Dravet Syndrome
Dr. Baraban and his team are using Dravet syndrome zebrafish mutants to screen and identify novel pharmacological treatments for Dravet syndrome patients. Zebrafish are commonly used in research due to their genetic and experimental accessibility. This project was the starting point for Dr. Baraban’s newest research project (see below) recently co-funded by the DSF and CURE.
Scott Baraban, PhD
CURE & DSF Research Award – $250,000 (2 year project)
Gene Profiling and High-Throughput Drug Screening in a Zebrafish Model of Dravet Syndrome
Pediatric epilepsies are associated with developmental or cognitive co-morbidities and are not well controlled by available drugs. Unfortunately, existing drug discovery programs are not designed to address this problem, as they are primarily based on acute or acquired seizures in adult rodent models of the epilepsies. Dr. Baraban seeks to shift current research in the epilepsy field in two ways. First, by utilizing immature zebrafish models designed to mimic known single-gene mutations seen in children (for example, Dravet syndrome), he will establish a drug discovery program targeted at pediatric epilepsy that also incorporates large-scale microarray gene analysis. Second, by focusing on the zebrafish model, he will establish a new template for high-throughput cost-effective drug screening with distinct advantages over current rodent-based approaches.
OPKO Health, Inc.
DSF Research Award – $250,000 (1st year of project grant)
More than 75% of children who have been diagnosed with Dravet syndrome have a defective SCN1A gene. As a result, the defective gene is not producing enough functional protein, leading to a diseased state. OPKO Health, Inc., a South Florida based pharmaceutical company, has developed new technology to increase SCN1A protein production. Early tests have shown a promising increase in this protein level in a Dravet patient’s fibroblast and in human cell lines, such as a neuroblastoma. This research is applicable to all mutation types. OPKO is committed to further the development of this work and to seek health authorities’ approvals worldwide. This project is overseen by Dr. Jane Hsiao, a grandparent of a child with Dravet syndrome. The DSF and collaborating organizations will fund a portion of this project to assist in lowering final patient treatment cost.
2010 Awards
Sooky Koh, MD, PhD
DSF Research Award – $100,000 (1 year project)
Novel Therapies to Block Epileptogenesis in Dravet Syndrome Mice
Using a mouse model of Dravet syndrome, Dr. Koh and her colleagues will investigate three novel strategies to treat Dravet syndrome and understand epileptogenesis, the process by which the developing brain evolves to produce repeated seizures. They will utilize anti-inflammatory therapy; use dietary interventions; and, finally, investigate the use of an enriched environment on the impact and outcome of seizures. The promise of this research program is in identifying treatments that minimize the detrimental effects of recurrent seizures, modify disease progression, and prevent chronic epilepsy.
Sebastian Maier, MD, PhD and Massimo Mantegazza, PhD
CURE & DSF Research Award – $150,000 (1 year project)
Cardiac arrhythmias and SUDEP in SMEI and other Nav1.1 (SCN1A) related epilepsies
Dravet syndrome is a severe and drug resistant form of epilepsy, characterized by high mortality rates. Sudden unexpected death in epilepsy (SUDEP) is the most frequent cause of death for individuals with Dravet syndrome. The majority of individuals with Dravet syndrome carry mutations in a sodium channel subtype that is found in the brain, heart and nerves. Drs. Maier and Mantegazza will study the role of this sodium channel subtype in the heart of a mouse model of Dravet syndrome in order to investigate the occurrence and mechanism of arrhythmias and their possible involvement in SUDEP.
Jack M. Parent, MD and Ian Miller, MD
ICE & DSF Research Award (co-funded for life of project)
International Dravet Syndrome/Ion Channel Patient Registry (IICEPR)
This patient registry, owned by the University of Michigan and Miami Children’s Hospital, collects basic information and genetic test results of individuals with Dravet syndrome and related epilepsies worldwide and is available to all interested researchers at no cost. The establishment of this registry will expedite future clinical trials and will serve to improve communication of ideas amongst interested researchers, as well as assure rapid distribution of any new information that may benefit patients and their families.